This study was designed to evaluate the effect of oral tolerance of caseins (CSN) and whey proteins (WP) in alleviating the allergic response to cow's milk proteins in Swiss albino mice raised on a milk protein–free diet. Oral tolerance was induced by feeding mice with 20 mg of CSN or WP once in a day for 4 days consecutively before immunization with respective protein by intraperitoneal (i.p.) injections (20 μg 200 per μl of PBS) using 2% of alum Al(OH)3 as adjuvant. Three weeks later, oral tolerance induction was analysed in humoral and cellular compartments of CSN- and WP-fed versus saline-fed control mice groups by measuring seric and intestinal antibody responses, mRNA abundance in splenic tissue and cytokine secretion patterns. The specific serum immunoglobulin-E (IgE) levels were significantly suppressed (p < 0.05), while sIgA was enhanced in these groups when compared with their respective saline-fed mice. Moreover, the mRNA levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in both CSN- and WP-tolerized mice were found to be significantly decreased, while the abundance of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) was increased significantly, as compared to respective control groups. Finally, cytokine profiles indicated a reciprocal decrease in IL-4 and IFN-γ versus an increase in IL-10 secretions in supernatants of cultured splenocytes of tolerized mice. Taken together, these results clearly showed that oral administration of cows' milk caseins and whey proteins can induce significant hyposensitization in mice, with the participation of suppressor cytokines.